Oxalyl chloride → HCID 25171033, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (2 g, 6.53 mmol, INTERMEDIATE 2) in dichloromethane (25 ml) were added oxalyl chloride (9.79 ml, 19.59 mmol) and a drop (ca. 10 μl) of dimethylformamide. The mixture was stirred for 1 h at 25° C., at which point a clear solution formed. The mixture was concentrated and then co-concentrated with 5 ml of toluene. To a solution of the residue in dichloromethane (25 ml) was added 4-aminomethyl-1-N-Cbz-piperidine (2 g, 8.05 mmol) and diisopropylethylamine (1.711 ml, 9.79 mmol). The mixture was stirred overnight at 25° C. and then concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 65i column, eluting with 1 column volume of 10% ethyl acetate in hexanes followed by a gradient of 10 to 100% ethyl acetate in hexanes over 10 column volumes to provide the title compound (2.53 g, 72.2%). Mass spectrum (ESI) 537.0 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.29 (m, 2H), 7.94 (d, J=8.5 Hz 2H), 7.90 (m, 1H), 7.49 (s, 1H), 7.27-7.35 (m, 4H), 6.69 (m, 1H), 5.11 (s, 2H), 4.09-4.30 (m, 2H), 3.31-3.49 (m, 3H), 2.79 (m, 2H), 1.86 (m, 1H), 1.77 (m, 2H), 1.45 (d, J=6.5 Hz, 6H), 1.18-1.30 (m, 2H).

Provenance & Evidence